Chlorine in PDB 4aoj: Human Trka in Complex with the Inhibitor Az-23

All present enzymatic activity of Human Trka in Complex with the Inhibitor Az-23:
2.7.10.1;

The structure of Human Trka in Complex with the Inhibitor Az-23, PDB code: 4aoj was solved by T.Wang, M.L.Lamb, M.H.Block, A.M.Davies, Y.Han, E.Hoffmann, S.Ioannidis, J.A.Josey, Z.Liu, P.D.Lyne, T.Macintyre, P.J.Mohr, C.A.Omer, T.Sjogren, K.Thress, B.Wang, H.Wang, D.Yu, H.Zhang, with X-Ray Crystallography technique. A brief refinement statistics is given in the table below:

Resolution Low / High (Å)	40.00 / 2.75
Space group	I 2 2 2
Cell size a, b, c (Å), α, β, γ (°)	130.727, 158.419, 152.577, 90.00, 90.00, 90.00
R / Rfree (%)	22 / 24.2

The structure of Human Trka in Complex with the Inhibitor Az-23 also contains other interesting chemical elements:

Fluorine	(F)	3 atoms
Zinc	(Zn)	6 atoms

The binding sites of Chlorine atom in the Human Trka in Complex with the Inhibitor Az-23 (pdb code 4aoj). This binding sites where shown within 5.0 Angstroms radius around Chlorine atom.
In total 3 binding sites of Chlorine where determined in the Human Trka in Complex with the Inhibitor Az-23, PDB code: 4aoj:
Jump to Chlorine binding site number: 1; 2; 3;

Chlorine binding site 1 out of 3 in the Human Trka in Complex with the Inhibitor Az-23


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 1 of Human Trka in Complex with the Inhibitor Az-23 within 5.0Å range: probe atom residue distance (Å) B Occ A:Cl900 b:33.7 occ:1.00 CL1 A:V4Z900 0.0 33.7 1.0 C17 A:V4Z900 1.8 30.0 1.0 C16 A:V4Z900 2.7 29.1 1.0 C7 A:V4Z900 2.8 27.6 1.0 N1 A:V4Z900 3.1 26.6 1.0 O A:MET592 3.3 35.0 1.0 N A:GLY595 3.5 29.6 1.0 CA A:GLY595 3.6 28.2 1.0 O A:ARG593 3.6 35.0 1.0 CD2 A:LEU516 3.7 34.3 1.0 C A:ARG593 3.8 34.3 1.0 N5 A:V4Z900 3.9 31.4 1.0 N2 A:V4Z900 4.0 30.0 1.0 CA A:ARG593 4.1 35.2 1.0 CE1 A:TYR591 4.2 30.3 1.0 CD1 A:LEU516 4.3 33.7 1.0 C A:MET592 4.3 34.8 1.0 N A:HIS594 4.4 32.7 1.0 C6 A:V4Z900 4.4 28.9 1.0 C8 A:V4Z900 4.4 31.1 1.0 CG A:LEU516 4.4 34.7 1.0 C A:HIS594 4.4 32.0 1.0 CB A:LEU516 4.5 37.3 1.0 N A:ARG593 4.7 34.7 1.0 CA A:HIS594 4.8 32.1 1.0 CD1 A:TYR591 4.9 30.8 1.0

Chlorine binding site 2 out of 3 in the Human Trka in Complex with the Inhibitor Az-23


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 2 of Human Trka in Complex with the Inhibitor Az-23 within 5.0Å range: probe atom residue distance (Å) B Occ B:Cl900 b:37.5 occ:1.00 CL1 B:V4Z900 0.0 37.5 1.0 C17 B:V4Z900 1.7 33.0 1.0 C16 B:V4Z900 2.6 30.8 1.0 C7 B:V4Z900 2.7 30.6 1.0 N1 B:V4Z900 3.0 26.8 1.0 O B:MET592 3.4 34.9 1.0 N B:GLY595 3.6 37.8 1.0 CA B:GLY595 3.6 37.1 1.0 O B:ARG593 3.7 39.1 1.0 N5 B:V4Z900 3.9 30.3 1.0 N2 B:V4Z900 4.0 31.0 1.0 CD2 B:LEU516 4.0 38.5 1.0 CE1 B:TYR591 4.0 36.2 1.0 C B:ARG593 4.0 37.8 1.0 C6 B:V4Z900 4.3 29.3 1.0 C8 B:V4Z900 4.4 32.2 1.0 CB B:LEU516 4.4 41.1 1.0 CD1 B:LEU516 4.4 39.9 1.0 C B:MET592 4.4 35.4 1.0 CA B:ARG593 4.4 37.6 1.0 CG B:LEU516 4.5 40.6 1.0 O B:HOH2002 4.5 47.0 1.0 C B:HIS594 4.5 38.5 1.0 N B:HIS594 4.6 38.0 1.0 OH B:TYR591 4.7 40.1 1.0 CD1 B:TYR591 4.8 34.1 1.0 CZ B:TYR591 4.8 38.0 1.0 N B:ARG593 4.9 35.7 1.0

Chlorine binding site 3 out of 3 in the Human Trka in Complex with the Inhibitor Az-23


Mono view


Stereo pair view

A full contact list of Chlorine with other atoms in the Cl binding site number 3 of Human Trka in Complex with the Inhibitor Az-23 within 5.0Å range: probe atom residue distance (Å) B Occ C:Cl900 b:39.3 occ:1.00 CL1 C:V4Z900 0.0 39.3 1.0 C17 C:V4Z900 1.7 33.1 1.0 C16 C:V4Z900 2.6 31.8 1.0 C7 C:V4Z900 2.7 33.0 1.0 N1 C:V4Z900 3.0 30.5 1.0 O C:MET592 3.4 42.7 1.0 CA C:GLY595 3.5 44.1 1.0 N C:GLY595 3.6 45.2 1.0 O C:ARG593 3.7 47.7 1.0 CD2 C:LEU516 3.8 40.0 1.0 N5 C:V4Z900 3.9 31.5 1.0 N2 C:V4Z900 4.0 32.8 1.0 C C:ARG593 4.0 46.7 1.0 CE1 C:TYR591 4.0 42.8 1.0 CD1 C:LEU516 4.2 41.5 1.0 CB C:LEU516 4.3 40.2 1.0 CG C:LEU516 4.3 41.2 1.0 C6 C:V4Z900 4.3 29.2 1.0 C8 C:V4Z900 4.4 31.0 1.0 C C:HIS594 4.4 46.9 1.0 CA C:ARG593 4.4 46.6 1.0 C C:MET592 4.4 43.5 1.0 N C:HIS594 4.6 46.8 1.0 OH C:TYR591 4.6 45.4 1.0 CZ C:TYR591 4.8 42.6 1.0 CD1 C:TYR591 4.9 40.5 1.0 C C:GLY595 4.9 44.6 1.0 N C:ARG593 5.0 44.5 1.0 CA C:HIS594 5.0 47.2 1.0 N6 C:V4Z900 5.0 30.6 1.0

T.Wang, M.L.Lamb, M.H.Block, A.M.Davies, Y.Han, E.Hoffmann, S.Ioannidis, J.A.Josey, Z.Liu, P.D.Lyne, T.Macintyre, P.J.Mohr, C.A.Omer, T.Sjogren, K.Thress, B.Wang, H.Wang, D.Yu, H.Zhang. Discovery of Disubstituted Imidazo[4,5-B]Pyridines and Purines As Potent Trka Inhibitors Acs Med.Chem.Lett. V. 3 705 2012.
ISSN: ISSN 1948-5875
PubMed: 24900538
DOI: 10.1021/ML300074J